Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients

  • Anskar Y. H. Leung
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.
  • Howard C. H. Chow
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.
  • Y. L. Kwong
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.
  • Albert K. W. Lie
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.
  • Alvin T. K. Fung
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.
  • W. H. Chow
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.
  • Alex S. B. Yip
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.
  • Raymond Liang
    From the Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong.

抄録

<jats:title>Abstract</jats:title> <jats:p>CYP2C9 polymorphisms reported in Caucasians (Arg144Cys in exon 3 and Ile359Leu in exon 7) are extremely uncommon in Chinese persons. The genotype of CYP2C9 in this population was characterized to investigate its relation with the interindividual variation in warfarin dosages. Eighty-nine Chinese patients receiving warfarin were recruited. Target sequences inCYP2C9 in exons 1, 4, and 5 were amplified by polymerase chain reaction, followed by direct sequencing. Polymorphisms at 4 positions were demonstrated in exon 4. Heterozygosities for 608TTG&gt;GTG (Leu208Val), 561CAG&gt;CCG (Gln192Pro), 537CAT&gt;CCT (His184Pro), and 527ATT&gt;CTT (Ile181Leu) existed at frequencies 0.75, 0.20, 0.10, and 0.09, respectively. Seventeen patients (frequency, 0.19) were homozygous for Val208. The common genotypic combinations at these loci are Ile181/His184/Gln192/Leu208Val (n = 50), Ile181/His184/Gln192/Val208 (n = 15), Ile181/His184/Gln192/Leu208 (n = 4), Ile181/His184/Gln192Pro/Leu208Val (n = 6), Ile181/His184Pro/Gln192Pro/Leu208Val (n = 4), and Ile181Leu/His184/Gln192Pro/ Leu208Val (n = 4). At codon 208, heterozygous Leu208Val and homozygous Val208 appeared to have a lower warfarin dose requirement than the homozygous Leu208. Patients who are heterozygous for Ile181Leu had a higher warfarin dose requirement than the homozygous Ile181. Amplified sequences in exons 1 and 5 did not exhibit polymorphism. In conclusion, Chinese patients showed genetic polymorphisms of CYP2C9 in exon 4 and at codon 208; most were heterozygous Leu208Val and homozygous Val208. Homozygous Leu208, a common allele in Caucasians, is uncommon in this cohort. The significance of these CYP2C9 polymorphic alleles remains to be determined.</jats:p>

収録刊行物

  • Blood

    Blood 98 (8), 2584-2587, 2001-10-15

    American Society of Hematology

被引用文献 (3)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ